反应详情

To toluene (1 ml) are added 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (62 mg) and palladium acetate (II) (16 mg) and the mixture is stirred under nitrogen atmosphere at room temperature for 5 minutes. To the mixed solvent is added the mixed solution of tert-butyl 4-{2-[(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-butyrate (200 mg), 1-bromo-3,5-bis-trifluoromethyl-benzene (126 mg) and toluene (1.5 ml), and the mixture is degassed under reduced pressure and thereto is added sodium tert-butoxide (51 mg) and the mixture is stirred under nitrogen flow at 80° C. overnight. The reaction solution is allowed to cool to room temperature, and thereto is added a saturated brine, and the mixture is extracted with ethyl acetate, and the organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by NH-silica gel column chromatography (hexane:ethyl acetate=10:1) to give tert-butyl 4-{2-[(3,5-bis-trifluoromethyl-phenyl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-butyrate (204 mg). MS (m/z): 772 [M+H]+

1. customthe mixture is degassed under reduced pressure
2. additionis added sodium tert-butoxide (51 mg)
3. stirringthe mixture is stirred under nitrogen flow at 80° C. overnight
4. temperatureto cool to room temperature
5. additionis added a saturated brine
6. extractionthe mixture is extracted with ethyl acetate
7. washthe organic layer is washed with a saturated brine
8. dry with materialdried over magnesium sulfate
9. concentrationconcentrated under reduced pressure
10. customThe resulting residue is purified by NH-silica gel column chromatography (hexane:ethyl acetate=10:1)